Nociception describes how potentially harmful stimuli are encoded, modulated, and conveyed to the sensory cortex. Noxious stimuli cause firing of primary sensory neurons, which synapse on secondary neurons in the dorsal horns of the spinal cord gray matter. Further transmission via the spinothalamic tract (STT) is modulated in the dorsal horn by a descending inhibitory pathway arising from the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM). If modulatory control of nociception is damaged, pain can be experienced without an appropriate cause, profoundly affecting quality of life. This neuropathic pain is a common but poorly- understood consequence of many neurological disorders, including multiple sclerosis and cervical spondylotic myelopathy. The overall hypothesis of this project is that dysfunction of this descending modulatory circuit, mediated by the loss of microstructural integrity in spinal cord white matter tracts, is a root cause of neuropathic pain. To investigate this, we will optimize functional and diffusion magnetic resonance imaging (fMRI and dMRI) methods for use in the brainstem and spinal cord at 7 T, quantify the blood oxygenation level- dependent (BOLD) signal in the cervical spinal cord gray matter in response to noxious thermal stimuli delivered to the arm, and identify white matter tracts in which abnormalities in diffusion MRI parameters (indicating microstructural degradation) correlate with abnormal pain modulation, as measured by quantitative neurosensory testing, clinical examination, and fMRI. This combination of functional and diffusion MRI measurements and quantitative neurosensory testing will provide new insight into the location of the white matter tracts carrying descending modulatory drive from the brainstem to the spinal cord, and allow us to investigate whether and how damage to these tracts impacts pain levels. This career development project also includes a training plan designed to refine and address gaps in the applicant?s technical and scientific knowledge and experience, develop his research career skills, expose him to the neuroimaging community, and lay the groundwork for his career as an independent scientist. The training plan encompasses: coursework in in biostatistics, pathophysiology of neurological and psychiatric disorders, clinical neuroscience, research grant applications, and budget management; presentation of his work at technical MRI and neuroscience conferences; delivery of formal classroom lectures and small-group teaching sessions; mentorship of research volunteers; organizing a research symposium; and hands-on training during the conduct of the research project. The Icahn School of Medicine at Mount Sinai is the ideal environment for this career development project. The combination of the Translational and Molecular Imaging Institute?s state of the art imaging resources and expert faculty, the Mount Sinai Hospital?s world-class clinical centers and their respective clinical and research faculties, and the school?s strong emphasis on translational research all contribute to this project?s enormous training potential and very high probability of success.